Several problems are known to be associated with per-oral delivery of pharmaceuticals where the pharmaceutical is swallowed and passes through the gastro-intestinal system.
One major problem with per-oral delivery is metabolic breakdown of the pharmaceuticals as they pass through the gastro-intestinal tract. Metabolic processes may cause the drug to break down into non-active or even harmful metabolites. This means that the required therapeutic dose will be unnecessarily large and that unwanted side effects may occur. A further disadvantage is that it is difficult to optimize the dose on an individual basis. In addition, for some pharmaceuticals, metabolic breakdown makes it unsuitable to use oral delivery.
The risk of deliberate or inadvertent overdosing is also a concern as the required therapeutic dose must be higher than the theoretically required dose in order to compensate for metabolic breakdown.
An orally ingested drug will also require a relatively long time before any effect of the drug is noticed. This means that where a quick response is particularly important such as with pain killers or drugs for motion sickness, there is a strong need for a better delivery system.
Nausea and vomiting may also prohibit uptake of a drug when administered orally. Migraines and motion sickness which are accompanied by such symptoms are examples of conditions where it is often too late for ingested drugs to have an effect once the symptoms have set in.
In order to overcome the deficiencies of oral delivery, it has previously been suggested to use injections, or sprays delivered to the oral or nasal cavity. A further alternative method is anal delivery. All these delivery methods suffer from drawbacks such as being technically complicated, unduly expensive, unpleasant, or painful.
Furthermore, it has been proposed to administer pharmaceutical agents by means of tablets which dissolve in the oral cavity and release the pharmaceutical agent. Such a tablet is disclosed in EP 1 295 595 A1. However, tablets disintegrating in the mouth suffer from a considerable drawback in that the uptake rate of pharmaceutical agents through the oral mucosa may be too low and that a smaller or larger proportion of the pharmaceutical agent may be inadvertently swallowed by the treated person. Further, when administering a pharmaceutical agent by means of tablets, the tablets will necessarily contain additional substances such as fillers, flavouring, etc. admixed with the active substance. When the tablets contain a small amount of active substance, it is a problem to achieve uniform distribution of the active substance in the tablets so that all tablets contain the same amount of active substance.
With the tablets in EP 1 295 595 A1, the exact dose that is actually administered on each occasion cannot be controlled. Consequently, there is a risk that the administered dose is too low to have the desired effect on the treated individual or too high if the tablet accidentally contains more active substance than intended. Moreover, problems associated with metabolic breakdown of pharmaceuticals may also occur. In order to alleviate the problem of absorption of the pharmaceutical via swallowed saliva it has been suggested in US2007/0031502 A1 to mix a pharmaceutically active agent with a bioadhesion or mucoadhesion promoting compound.
However, there still remains a need for an improved and simplified delivery system that can be used with a broad range of bioactive substances including such substances that cannot be ingested without suffering metabolic degeneration and that solves the problems of accurate dose delivery even of small doses of bioactive substances.